The present invention relates to chelating agents, in particular to chelating agents exhibiting selectivity for tri-valent (manganic) manganese ions, to the corresponding manganic chelates, and to their use for the treatment of manganese deficiency in plant cultivation.
Manganese deficiency is a common problem in agriculture, in field crops as well as in fruit orchards, gardening, and other forms of plant cultivation.
As a remedy some soils may be treated with manganese salts, usually the sulphate, but the manganese soon forms insoluble oxides which are no longer available to the plants. xe2x80x9cBandedxe2x80x9d application is therefore recommended, whereas general or broad-cast application is ineffective. In most cases manganese deficiency instead is treated or prevented by foliar application of manganese sulphate.
In the case of other microelements, e.g. Iron, deficiencies often are more conveniently treated by general soil application, such as broadcasting or drip irrigation. The metal is kept soluble in the form of a suitable chelate. It has long been desired to find a manganese chelate of such utility. Attempts to use ordinary manganese (Mn2+) chelates of known chelating agents like EDTA and DTPA have proved counter-productive, the problem being that the chelating agent is taken over by ferric iron ions from the soil and the manganese set free is soon oxidised to insoluble oxides.
An object of the present invention is to provide a manganic chelate with a high stability with regard to ferric iron ions and other metal ions present in the soil and with regard to decomposition by hydrolysis and, more particularly, to provide a manganic chelate which remains unchanged for an effective period and can therefore be used for the treatment of manganese deficiency by general application to soil and other growing substrates.
The chelating agents (chelants) according to the present invention have the general structure: 
wherein: n=2-4
whereby
at least two of X are of formula III
Y=COOH, xe2x80x94PO3H2 or o-hydroxyphenyl
R1, R2 and R3 are independently H or C1-C8 alkyls
m=0-3, preferably m=1, 2 or 3, and most preferably m=1
Z and Zxe2x80x2 are unsubstituted or substituted C
C*=C or CH or N
Z1, Z2, Zxe2x80x21 and Zxe2x80x22 are independently selected from H (or nothing for Z2 and Zxe2x80x22 if C* is N) and C1-C10 groups that optionally contain one or more N atoms (optionally attached directly to C*), whereby one of the pairs Z/Z1, Z/Z2 and Z1/Z2 and one of the pairs Zxe2x80x2/Zxe2x80x21, Zxe2x80x2/Zxe2x80x22 and Zxe2x80x21/Zxe2x80x22 may be connected to form substituted or unsubstituted (hetero)(poly)cyclic structures of less than 20 atoms.
C* is either part of an aromatic (hetero)(poly)cyclic structure or linked by a double bond to Z or Z2 and/or Zxe2x80x2 or Zxe2x80x22,
These aromatic cyclic structures or double bonds ate preferably conjugated with the respective Cxe2x95x90N bonds to allow each N atom to share the negative charge resulting from dissociation of the OH group.
The inventors have surprisingly found that the hexadentate chelating agents according to the present invention are highly selective chelants for manganic ions in the presence of ferric iron ions and that the manganic chelates also exhibit a remarkable stability with regard to hydrolysis, as well as a good ability to remain soluble in the presence of an iron-containing soil.
More specifically, the manganic chelates according to the present invention have been found to form stable solutions up to a pH of 10.5-11, indicating a pKa for hydrolysis of at least about 11. The ferric chelates of the same chelating agents exhibit stability up to a pH of about 8-9.
Alkaline, neutral or weakly acidic soils are usually more or less aerated. When manganese is applied to such a soil, it will slowly, but inevitably be oxidised to insoluble manganese dioxide. However, if the manganese is very strongly chelated, it can, in principle, be kept soluble and available to the plants for a sufficient time, e.g. weeks or months.
To uphold such strong chelation of manganese ions requires high stability of the chelate with regard to hydrolysis, especially at a high soil pH. At least as important is a high stability with regard to other metal ions that may compete for the chelant and thereby set free manganese ions. This problem is especially critical and well-known with ferric iron ions, which tends to be abundant in soils. Due to its tri-valent positive charge, ferric iron ions is known to form very stable chelates with most chelating agents, e.g. EDTA or DTPA. For manganese, the normal state is the divalent manganous cation, which forms chelates of much lower stability than ferric iron ions. Consequently, it is well-known that manganous chelates when applied to soil are rapidly decomposed, and made useless, by ferric Iron ions in the soil.
An interesting option would be to use a chelate of tri-valent (manganic) manganese, which is known to form some chelates of the same order of stability as ferric iron ions The phenolic chelating agents, e.g. EDDHA (EHPG), long used in the form of their ferric chelates on alkaline soils, would be candidates for forming manganic chelates of fair hydrolytic stability, but the inventors have found that in the presence of an iron-containing soil these manganic chelates will decompose rapidly.
This is in accordance with the findings reported by Ahrland, Dahlgren, and Persson (Acta Agric. Scand, 4:101-111, 1990). These authors report that manganic chelates generally are more prone to hydrolysis than ferric chelates. For manganic EDDHA (EHPG) a pKa value of 9.3 is reported for hydrolysis, whereas results according to the present invention indicate a corresponding pKa for the new chelates of at least 11. For ferric iron ions the situation is the reverse. A pKa value for hydrolysis of 12.7 is reported by the same authors, whereas the chelate according to the present invention has a pKa for ferric iron ions of about 9-10.
A manganic chelate with a stability of approximately the same order as that of the ferric chelate will allow a considerable proportion of manganic ions to be set free in the soil. A chelant is sought with a high selectivity for manganic ion over ferric ion. A very high stability of the manganic chelate is important, since the formation of insoluble manganese oxides will be accelerated by a so-called dismutation of two manganic ions to form one manganous ion and one mole of manganese dioxide. Certain soil bacteria also promote the oxidation of soil manganese to the dioxide.
Not wishing to be bound by any theory, the inventors believe the selectivity of the chelating agents according to the present invention to be found in the distorted configuration of the manganic ion in many of its compounds. While the ferric ion always prefers to co-ordinate in a regular octahedral (hexadentate) fashion, the manganic ion is known to display so-called Jahn-Teller distortion. The effect is that two opposite (xe2x80x9caxialxe2x80x9d) bonds tend to be elongated in comparison with the remaining four (xe2x80x9cequatorialxe2x80x9d) bonds. It is thought, in order to explain the selectivity of the chelating agents according to the present invention, that the two positions where the axial coordinating groups branch out are more or less locked by a rigid structure including the four equatorial bonds. With such restrictions on the two axial coordinating groups, the importance of the elongated manganic valences is understandable.
The Drawings that are provided herewith further elucidate the present invention wherein:
FIG. 1 illustrates the salicylaldehyde-ethylenediamine structure of the manganic chelates of the invention;
FIG. 2 depicts a chelate structure showing the two carboxymethyl groups on the Nxe2x80x94N bridge;
FIG. 3 shows the chelate illustrated in FIG. 2 in a two dimensional manner;
FIG. 4 illustrates hydroxy-imine variant structures for the chelate;
FIG. 5 shows soil test results for the chelate of this invention and other manganese sources; and
FIG. 6 depicts a synthesis route to make a particular manganese selective chelate embodiment of the present invention.
In one of the preferred manganic chelates of the invention the rigid, equatorial structure is thought to be formed by the phenolic and iminic groups in the well-known salen structure (short for salicylaldehyde-ethylenediamine adduct), which is known to prefer a stable, planar structure in its metal chelates, as shown in FIG. 1.
The negative charges are partly delocalised from the phenolic oxygen to the imine nitrogen. This resonance serves to favour the rigid, planar structure. The complete chelate has two carboxymethyl groups on the Nxe2x80x94N bridge (FIG. 2).
Said Nxe2x80x94N bridge may be formed by the condensation of one molecule of 3,4-diamino-1,6-hexanedioic acid with two molecules of salicylaldehyde. Due to the rigid salen structure the two carboxymethyl groups are restricted in the ways in which they can occupy the two axial valences of the metal ion. This is most probably the feature that favours the elongated axial valences of the manganic ion over those of the ferric ion.
The chelating agent of FIG. 2 is depicted in a 2-dimensional way in FIG. 3.
The two carbon atoms joining the nitrogen atoms are both asymmetrical, and the molecule can therefore occur in two diasterea-isomers. The one depicted in FIG. 3 is the racemic isomer, which is believed to be produced as described in Example 1 (see below). The moso-isomer will give rise to a different geometry, but may also be of value.
For comparison, the corresponding chelating agent with secondary amino functions instead of the imine groups was prepared by reduction with sodium borohydride (see below). The manganic chelate of the reduced product proved to be very unstable to hydrolysis. Manganese dioxide started to precipitate immediately at neutral pH.
In addition to the salen structure, other four-dentate chelating units containing two imine nitrogens and two hydroxylic anions can enclose the manganic ion in a similar way and form the basis of chelating agents with a corresponding selectivity to manganic ion. Some of the most elementary examples are those with various substituents in the two benzene rings, but more essential variations in the structure will also produce a similar effect. A moderate variation is the use of pyridoxal (2-methyl-3-hydroxy-5-hydroxymethyl-4-pyridinaldehyde) instead of salicylaldehyde. More substantial variations include the hydroxy-imines formed by such hydroxyoxo compounds as shown in FIG. 4.
With isatin (FIG. 4a) and tropolone (FIG. 4b) the 6-membered chelate rings of the salen structure will be replaced by likewise resonance-stabilised 5-membered chelate rings. The chelates will comply with the general structure II shown earlier.
Another variation is to use a different diamino diacid as the central building block in the di-imine structure. While 3,4-diamino-1,6-hexanedioic acid has a two-carbon chain joining the two nitrogens, it is possible within the scope of the invention to increase this chain length to 3 or even 4 while still retaining an adequate stability and rigidity of the structure (n=2-4 in the general structure defined).
It is also possible to modify the positioning of the two carboxyl groups that will form the two axial bonds. This can be done by varying the length of the chains that connect the two carboxyl groups to the carbons linking the two nitrogen atoms. This chain length, with m=1 in the chelant made from 3,4-diamino-1,6-hexanedioic acid, can be varied from 0 to 3 while still retaining the interaction with the elongated axial valences of the manganic ion. Preferably m=1, 2, or 3. Most preferably m=1.
A final type of variation in the chelating agent of the invention is replacing the carboxyl groups with other acidic coordinating groups such as phosphonyl (xe2x80x94PO3H) or 2-hydroxy-phenyl.
A synthesis route for a further manganese selective chelate according to the present invention is shown in FIG. 6.
The experimental hydrolytic stability of the new manganic chelates was demonstrated in a shaking test with calcium carbonate in which the new manganic chelate stayed completely soluble for at least several weeks.
The inventors demonstrated the selectivity of the new chelating agents by means of comparative experiments with ferric and manganic ions at near neutral pH. The new chelant showed a remarkable preference for manganic ion, as shown by the yellow colour remaining stable for at least several weeks.
Consequently, the new manganic chelate has the qualities required for soil application. This has been demonstrated in comparative tests with other manganese chelates using an actual Iron-containing soil. Dilute solutions of the new manganic chelate and of the other manganese sources were treated with a typical soil having a low manganese content but a high iron content. With the new manganic chelate the soluble manganese decreased very slowly and retained about 50% of its original content after 19 days, whereas all the other Mn chelates tested were largely insolubilised after 1-2 days.
The soil tests demonstrate that the new manganic chelates will remain dissolved in the water phase of the soil. They will therefore be mobile and will be able to migrate and reach the roots of plants. The roots will most certainly be able to absorb the manganese in the divalent (manganous) form after creating a local reducing environment and lowered pH. This is the strategy plants are known to use to destabilise chelates of ferric iron ions and absorb the iron.
The products of the invention and the results obtained are further detailed in Examples 1-8.
The di-imine chelating agents of the invention were prepared by the condensation of one molecule of an appropriate diamino compound, having two acidic groups attached as defined above, with two molecules of a suitable hydroxy-oxo compound as defined above, or a suitable derivative thereof.
The manganic chelates can be produced using an already tri-valent manganese salt such as the acetate, Mn(OAc)3. An alternative method is to first prepare a manganous chelate by the use of, e.g., manganous sulphate and then to oxidise to the manganic state with air or by adding an oxidant such as potassium permanganate or manganese dioxide.